Core C, Genomics, applies a battery of conceptually related technologies to the samples from the Projects. The first is microarray analysis of gene expression, a methodology that is standard and extensively utilized in our laboratories. This consists of two interactive components: the fabrication of the arrays, their quality control, and the scanning of the hybridized arrays by the Albert Einstein Microarray Facility, of which ugenlicht is chairman of the Oversight committee; and the conduct of the experiments (probe preparation, hybridization, and initial data base generation and analysis) in Augenlicht's laboratory/array facility. We have extensive experience in conduct of such experiments and data analysis, including application of standard data filtering, clustering algorithms, methods of validation and functional follow-up, and basic statistical methods. We also already interact extensively in analysis of such data bases with the Biostatistics Core (D). The second technology in this Core is analysis of DNA methylation, both of individual loci, and by genome wide scanning using methylation arrays. This is under the direction of Judith Christman at the University of Nebraska Medical School. The data from this portion of the Core will dissect the extent to which altered gone expression is linked to altered gene methylation, of particular interest due to our utilization of the nwdiet#1 which is deficient in methyl donors. The third aspect of this Core is a novel method of imaging of transcription sites for specific genes developed at Einstein by Robert Singer, who collaborates with Augenlicht extensively on other projects. This unique methodology allows us to address details of mechanism of transcriptional regulation (Project 2), as well as to image and quantify expression of multiple genes simultaneously in situ. Thus, this methodology, which provides a tool to profile expression in situ, can identify cells with unique profiles of expression within architecturally defined regions of the crypt-villous, and tumor, making it possible to identify and characterize minor cell populations with unique patterns of gene expression and therefore phenotype. The fourth technology in this Core is Structural Proteomics. This part of the core capitalizes on two unique facilities: first, the fact that Einstein, under the direction of Mark Chance, owns and operates 2 high-energy beam lines at Brookhaven National Laboratory, making it possible to solve the three dimensional structure of proteins rapidly; second, this is coupled in Chance's laboratory, and through consortiums of which he is a part, to methodology for high throughput sequence sub-cloning, expression, translation, and protein crystallization. Thus, when confronted with sequences with highly informative and interesting expression patterns from Projects 1 and 3, but for which there is no known (or implied) function, we will be able to efficiently generate three dimensional structural data for the encoded protein to guide our understanding and design of future experiments.